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Jones et al. Hereditary Cancer in Clinical Practice 2013, 11:19 
http://www.hccpjournal.eom/content/1 1/1/19 



HEREDITARY CANCER 
IN CLINICAL PRACTICE 



RESEARCH Open Access 



The impact of genetic variants in 
inflammatory-related genes on prostate cancer 
risk among men of African Descent: a case control 
study 

Dominique Z Jones 1 , Camille Ragin 2 , Nayla C Kidd 1 , Rafael E Flores-Obando 3 , Maria Jackson 4 , 
Norma McFarlane-Anderson 5 , Marshall Tulloch-Reid 6 , Kevin S Kimbro 7 and LaCreis R Kidd 1 * 



Abstract 

Purpose: Although case-control studies have evaluated the role of variant inflammatory-related loci in prostate 
cancer, their impact is virtually unknown among men of African descent. To address this, we evaluated the impact 
of inflammatory cytokine single nucleotide polymorphisms (SNPs) on prostate cancer risk for men of African 
descent. 

Methods: Forty-four SNPs in inflammatory cytokine-associated genes were evaluated among 814 African-American 
and Jamaican men (279 prostate cancer cases and 535 controls) using lllumina's Golden gate genotyping system. 
Individual SNP effects were evaluated using logistic regression analysis. 

Results: Four SNPs were modestly associated with prostate cancer after adjusting for age. In the total population, 
inheritance of the IL1R2 rsl 1 886877 AA, 1L8RB rsl 1 574752 AA, TNF rs1 800629 GA + AA, and TNF rs673 GA genotypes 
modestly increased prostate cancer risk by 1.45 to 1 1.7-fold relative to the referent genotype. Among U.S. men, 
age-adjusted dominant, recessive and additive genetic models for the IL1R2 rsl 1886877 locus were linked to an 
increase in prostate cancer susceptibility. However, these main effects did not persist after adjusting for multiple 
hypothesis testing. 

Conclusion: Our preliminary data does not strongly support the hypothesis that inflammatory-related sequence 
variants influence prostate cancer risk among men of African descent. However, further evaluation is needed to 
assess whether other variant inflammatory-related genes may contribute to prostate cancer risk and disease 
progression in larger and ethnically diverse multi-center studies. 

Keywords: Prostate cancer, Inflammatory-related sequence variants, Single nucleotide polymorphisms 



Introduction 

Chronic inflammation is thought to predispose an individual 
to cancer development [1]. This relationship is supported 
by a number of studies involving inflammatory bowel 
disease, colon cancer, hepatitis, liver cancer, pancreatitis, and 
pancreatic cancer [2-6]. Through several lines of evidence 
from epidemiological, histopathological, animal, genetic 
and molecular pathological studies, chronic inflammation 



* Correspondence: rkidd01@louisville.edu 

'Department of Pharmacology & Toxicology, University of Louisville, 
Louisville, KY, USA 

Full list of author information is available at the end of the article 



is also thought to play a major role in prostate cancer 
development [2,3]. For example, prostatic infections have 
been implicated in prostate cancer either through direct 
or indirect promotion of the inflammatory process [1-3]. 
In addition, the use of non-steroidal anti-inflammatory 
drugs (NSAIDS) and other anti-inflammatory agents have 
been shown to reduce prostate cancer risk [4]. 

The production of cytokines can be influenced by single 
nucleotide polymorphisms (SNPs) detected within pro- and 
anti-inflammatory genes. Genetic variations in cytokine 
related genes may lead to alterations in the spectrum of 
cytokines expressed in an inflammatory environment or 



© 201 3 Jones et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative 
BlOlVlGCl C^ntrs! Commons Attribution License (http//creativecomn ons.org/lii :nsi 1 hich perm ts unrestricted use, distribution, and 

reproduction in any medium, provided the original work is properly cited. 



Jones et al. Hereditary Cancer in Clinical Practice 2013, 11:19 
http://www.hccpjournal.eom/content/1 1/1/19 



Page 2 of 1 1 



level of antitumor response [5]. Epidemiological studies 
have reported on the relationship between prostate cancer 
susceptibility and genes involved in the cytokine-cytokine 
receptor signaling pathway, such as interleukins and their 
receptors, ribonuclease L (RNASEL) and tumor necrosis 
factor (TNF) [6-13]. While men of African Descent suf- 
fer disproportionately from this disease [2,3,14,15], there is 
limited information about the positive link between variant 
cytokine genes and prostate cancer development in this 
population [16,17]. Therefore, additional studies are 
needed to investigate the role of inflammatory-related SNPs 
in the development of prostate cancer among individuals of 
African Descent. 

The current study evaluated the impact of 44 inflamma- 
tory-related sequence variants in relation to prostate cancer 
risk among men of African Descent from the U.S. and 
Jamaica. Findings from our study will help to fill in the 
gaps in information pertinent to prostate cancer among 
men of African Descent. 

Materials and methods 

Study population 

Our study population, 279 cases and 535 controls, was 
comprised of two independent case-control study sets. 
These studies include the Prostate Cancer Clinical Out- 
come Study (PC 2 OS) at the University of Louisville and 
the Prostate Cancer Study in Jamaica at the University 
of the West Indies, Mona Campus. For both study sets, 
all incident prostate cancer cases were histologically 
confirmed and the controls were assigned based on normal 
PSA levels, and normal DREs/biopsies. Descriptions of each 
contributing study have been previously described [18,19]. 
Briefly, the PC 2 OS study included 170 incident pros- 
tate cancer cases and 433 controls recruited between 
2001-2005 through the Howard University Hospital (HUH) 
Division of Urology or related prostate cancer screening 
programs. Enrolled participants were men of African des- 
cent from the Washington, D.C. and Columbia, S.C. areas. 
The racial subgroups included self-reported African 
Americans, East African Americans, West African Americans, 
and Caribbean Americans. The Prostate Cancer Study 
in Jamaica included consecutively enrolled 109 incident 
prostate cancer cases and 102 controls recruited from 
2005-2007 through the Urology clinic at the University 
Hospital of the West Indies in Kingston Jamaica. 

Criteria for inflammatory gene and SNP selection 

Inflammatory-associated genes and SNPs were selected 
using one or more of the following criteria: (1) empirical 
evidence that supports a relationship between the SNP/ 
gene and cancer or inflammatory/immune response related 
diseases; (2) commonly studied loci; (3) marked disparities 
in genotype frequency comparing men of African Descent 
to their Caucasian counterparts (i.e., ±10% change); (4) 



evidence demonstrating a link with alterations in mRNA 
expression/stability or protein expression/structure or 
function using in silico tools such as SNPinfo (http:// 
snpinfo.niehs.nih.gov/snpinfo/snpfunc.htm) or published 
reports; and (5) a minor allele frequency >5% reported in 
the National Center for Biotechnology Information 
(NCBI) Entrez SNP, (http://www.ncbi.nlm.nih.gov/snp). 
According to NCBI, the selected SNPs had an average 
minor allele frequency of 22%. However, the IL1RN 
rs315951 SNP had an allele frequency of 2.1%. This rare 
non-synonymous sequence variant was included in the 
analysis to explore whether a rare SNP would lead to 
substantial gains in effect sizes (i.e., 2-3 fold increases 
in risk) and contribute to the missing genetic heritability 
[20,21]. 

Genetic analysis of variant inflammatory-associated SNPs 

Allelic discrimination of 44 inflammatory-associated se- 
quence variants was performed using a custom Illumina 
GoldenGate Genotyping assay with VeraCode Technology 
and BeadXpress reader, according to the manufacturer's 
instructions [22]. 

Statistical analysis 

Evaluation of the relationship between variant inflammatory 
associated alleles and prostate cancer risk was performed 
using univariate and multivariate analyses. The chi-square 
test of heterogeneity was used to assess for significant dif- 
ferences in the distribution of homozygous major, hetero- 
zygous, or homozygous minor genotypes between prostate 
cancer cases and controls. Evaluation of the relationship 
between prostate cancer risk and selected polymorphic 
genes, expressed as odds ratios (ORs) and corresponding 
95% confidence intervals (CIs), were estimated using 
unconditional multivariate LR models adjusted for age. The 
major or common genotype was used as the reference 
category for each LR model. Statistical significance was 
assessed using a Bonferroni Correction (a = 0.05/44 
SNPs) cut-off of 0.001, in order to adjust for multiple 
comparisons. All statistical analyses were performed using 
SAS 9.3 (SAS Institute Inc., Cary, NC) and SNP Variation 
Software 7.0 (Golden Helix, Bozeman, MT). 

Statistical power 

Based on our sample size for the total population, U.S. 
and Jamaican men, we had >80% power to detect 
SNPs with odds ratios (ORs) of >1.4, >1.6, >1.8, re- 
spectively, for a co-dominant genetic model with 1 
degree of freedom (df), a minor allele frequency of at 
least 22% and disease prevalence of 0.74%. Analyses 
were performed using Power for Genetic Association 
Version 2 Software [23]. 



Jones et al. Hereditary Cancer in Clinical Practice 2013, 11:19 
http://www.hccpjournal.eom/content/1 1/1/19 



Page 3 of 1 1 



Results 

Prevalence of inflammatory-associated sequence variants 
among men of African Descent 

Inheritance of variant inflammatory-related loci was fairly 
common among African- American men in the current 
study. Specifically, the minor allele frequencies of the 
44 sequence variants ranged from approximately 2.6% 
to 48%, as depicted in Table 1. Notably, the observed 
genotype frequency distribution among controls did not 
significantly deviate from expected counts according to 
the Hardy Weinberg equilibrium. With the exception of 
four loci {IL1RN rs4251961, IL10RB rs999788, IL10RB 
rs283416, and ILR1 rs3917225), the observed genotype 
frequencies in the current study corroborated with values 
for individuals of African-American/African ancestry 
reported in the NCBI's SNP entrez (P = 0.063-1.000), as 
shown in Table 1. 

Relationship between inflammatory sequence variants 
and prostate cancer risk 

Seven out of 44 sequence variants detected in inflamma- 
tory-related genes were modestly associated with prostate 
cancer risk among 814 men of African Descent (279 
cases and 535 controls), as summarized in Table 2. For 
age-adjusted risk models, elevations in prostate cancer 
susceptibility were observed among carriers of IL1R2 
rsll88687 7AA (OR = 1.92; 95%CI= 1.11, 3.32), IL8RB 
rsll574752 GA + AA (OR = 38.40; 95%CI = 3.86, 382.8), 
TNF rsl800629 GA + AA (OR = 1.53; 95%CI = 1.06, 2.20), 
and TNF rs673 GA (OR = 1.50; 95%CI = 1.04, 2.16) geno- 
types with risk estimates ranging from 1.50-38.4. The 
IL1R2 rsl 1886877 marker was the only genetic susceptibil- 
ity factor significant under the additive genetic model 
(P-trend = 0.010), indicative of a significant dose-response 
effect in relation to the number of inherited minor alleles. 
The aforementioned markers were not classified as im- 
portant prostate cancer risk indicators after adjusting for 
multiple comparisons bias using the Bonferroni correc- 
tion, with a significance cut-off of <0.001. 

Upon stratification by sub-population, modestly signifi- 
cant prostate cancer biomarkers varied by racial/ethnic 
group in the age adjusted risk models. Possession of the 
RNASEL rsl213524 AG genotype was associated with a 
2.17-fold increase in the risk of developing prostate cancer 
(OR = 2.10; 95%CI = 1.04, 4.24) among Jamaican men, as 
detailed in Table 3. However, this locus was not significant 
in the dominant, recessive or additive genetic models. 
Similar to the total population, inheritance of sequence 
variants in IL1R2, IL10RA and TNF among U.S. men were 
linked with a significant increase in prostate cancer risk. 
Among U.S. men, two inflammatory-related sequence var- 
iants, [IL1R2 rsl 1886877 (GA, GA + AA, AA) and IL10RA 
rs4252243 AA], were associated with a 1.82-2.49-fold in- 
crease in prostate cancer risk. Out of these 2 markers, the 



IL1R2 rsl 1886877 locus was significant for the dominant 
(OR = 2.75; 95%CI= 1.38, 5.50), co-dominant (OR = 1.82; 
95%CI=1.14, 2.88), recessive (OR = 2.05; 95%CI=1.10, 
3.80), and additive (P-trend value = 0.002) genetic models. 
None of the aforementioned markers survived correction 
for multiple hypotheses testing. Moreover, the IL10RA 
rs4252243 SNP was only significantly related to prostate 
cancer risk under the recessive genetic model (OR = 2.49; 
95%CI = 1.08, 5.72). 

Discussion 

Chronic inflammation has been associated with tumor 
development and metastasis. Inflammatory response is 
regulated through a complex network of cytokines, cyto- 
kine receptors and downstream targets that synergistically 
regulate innate/humoral immune and inflammatory pro- 
cesses. Recent molecular and genetic epidemiology studies 
have demonstrated that chronic inflammation and suscep- 
tibilities in inflammatory-associated genes are related to 
the development of several cancers, including lymphoma, 
and gastric and prostate cancer [6,16,24-26]. However, 
to our knowledge, there are few published reports on 
the impact of variant cytokine-related genes in relation to 
prostate cancer among men of African Descent. There- 
fore, the current study evaluated the individual effects of 
44 inflammatory associated sequence variants on prostate 
cancer risk among 279 cases and 535 disease-free men of 
African Descent from the U.S and Jamaica. Our findings 
revealed a modest increase in prostate cancer risk for un- 
adjusted and adjusted logistic regression models for IL1R2 
rsl 1886877 among men of African Descent. The additive, 
dominant and recessive genetic models of this variant 
were significant even after adjusting for age. However, this 
relationship did not survive after accounting for multiple 
comparisons bias. 

IL1R2 rsll886877 is about 2415 base pairs from the 
transcription start site, which suggest it may have a high 
likelihood of regulating IL1R2 gene expression. Currendy, 
there are no published reports on the relationship between 
IL1R2 rsl 1886877 and prostate cancer for any population. 
Although there is no evidence of the impact of this 
sequence variant on prostate cancer risk among European 
and African American men, the relationship between the 
IL1R2 gene expression and prostate cancer has been dem- 
onstrated through published reports [27-29]. Leshem and 
colleagues (2011) found that the promoter region oiILlR2 
possesses putative binding motifs for the TMPRSS2/ERG 
fusion gene, which is highly expressed in aggressive pros- 
tate cancer [27]. When the expression of IL1R2 was 
knocked down using small interfering RNAs, it resulted 
in the reduction of ZEB2 mRNA expression in hTERT/ 
shp53/CyclinD-CDK4 overexpressing cells exposed to 
TMPRSS2/ERG [25]. TMPRSS2/ERG fusion gene indir- 
ectly up-regulates ZEB2, a facilitator of the epithelial to 



Table 1 Functional consequence and prevalence of inflammatory-associated sequence variants 



dbSNPID Gene Location NCBI NCBI NCBI NCBI NCBI Current study Current 

functional nucleotide minor allele major/major major/minor minor/minor nucleotide study MAF 
consequence change frequency genotype genotype genotype change n(%) for 
(major > (MAF) for n (%) for n (%) for n (%) for (major > African- 
minor allelef African- African- African- African- minor allele) Americans 
Americans Americans Americans Americans 



Current 
study 

major/major 
genotype 
n (%) for 
African- 
Americans 



Current 
study 

major/minor 
genotype 
n (%) for 
African- 
Americans 



Current 
study 

minor/minor 
genotype 
n (%) for 
African- 
Americans 



Overall x 2 
P-value 
comparing 
genotypes from 
individuals of 
African Descent 
as reported in 
NCBI versus the 
current study™ 



rs1058867 T 

rsl 071 676* 

rs1 11 23902* 
rs 1126579* 

rs 1143627* 

rs 1143634* 

rsl 1574752* 

rs1 1886877 
rsl 21 35247* 

rsl 2328606* 

rsl 304037* 

rs16944* 

rs17561* 

rsl 799964* 
rsl 800587* 
rsl 800629* 
rsl 800871* 



L10RB 

L1B 

L1R2 
L8RB 

L1B 

L1B 

L8RB 

L1R2 
RNASEL 

L1R2 

L1A 

L1B 

L1A 

TNF 

ILIA 
TNF 

IL10 



UTR'3 
miRNA 

UTR'3 
miRNA 

Intron 1 

UTR'3 
miRNA 

Near gene 5' 
TFBS 

Exon 4 
Splicing 

UTR'3 
miRNA 

Intron 1 

UTR'3 

TFBS, miRNA 

Near gene 5' 
TFBS 

UTR'3 
miRNA 

Near gene 5' 
TFBS 

Exon 4 
Splicing, 
nsSNP, 
benign 

Near gene 5' 
TFBS 

UTR'5 

TFBS, Splicing 

Near gene 5' 
TFBS 

Near gene 5' 
TFBS 



G > A 

G>C 

A>C 
C>T 

C>T 

C>T 

G > A 

T>C 
C>T 
A > G 
A > G 
G >T 

T>C 
C>T 
G > A 
C>T 



A = 37.9 

C= 14.6 

C = 31.8 
T=14.5 

T = 37.5 

T= 12.9 

A = 1 0.4 

C= 16.3 
T=11.2 
G = 39.6 
G = 39.0 
T= 15.3 

C= 12.9 
T = 39.1 
A = 13.7 
T = 36.3 



26 (42.0) 
1 9 (79.2) 

10 (45.5) 

46 (74.2) 

1 2 (50.0) 

47 (75.8) 
19 (79.2) 

33 (67.3) 
38 (77.6) 

8 (33.3) 
18 (30.5) 
44 (71.0) 

46 (74.2) 

9 (39.1) 
46 (74.2) 
28 (45.2) 



25 (40.3) 
3 (12.5) 

10 (45.5) 
14 (22.6) 

6 (25.0) 

14 (22.6) 
5 (20.8) 

16 (32.7) 

11 (22.4) 
1 3 (54.2) 
36 (61.0) 

1 7 (27.4) 

16 (25.8) 
10 (43.5) 

1 5 (24.2) 
23 (37.1) 



11 (17.7) 
2 (8.3) 

2 (9.10) 

2 (3.20) 

6 (25.0) 
1 (1.60) 
0(0.00) 

0 (0.00) 

0 (0.00) 

3 (12.5) 
5 (8.50) 

1 (1.60) 

0 (0.00) 

4 (17.4) 

1 (1.60) 
11 (17.7) 



G > A 

G>C 

A>C 
G>A + 

G>A + 

G>A + 

G > A 

G > A 
A>G + 

G> A + 

A > G 
A > G 
C>A + 

A>G t 
G>A + 
G > A 
G> A + 



A = 33.9 

C=16.1 

C = 30.7 
A = 13.8 

A = 39.6 

A = 15.5 

A = 9.40 

A = 35.8 
G= 17.9 

A = 13.5 

G = 41 .1 

G = 45.1 

A = 18.6 



239 (44.6) 

378 (70.7) 

258 (48.2) 
402 (75.1) 

1 94 (36.3) 

381 (71.2) 

435 (81.3) 

211 (39.4) 
368 (68.8) 

405 (75.7) 

191 (35.7) 

1 56 (29.2) 

358 (66.9) 



229 (42.9) 

142 (26.5) 

225 (42.1) 
118 (22.1) 

256 (48.2) 

142 (26.5) 

99 (18.5) 

265 (49.5) 
142 (26.5) 

116 (21.7) 

248 (46.4) 

275 (51.4) 

1 55 (29.0) 



67 (12.5) 

1 5 (2.80) 

52 (9.70) 
1 5 (2.80) 

83 (15.5) 

1 2 (2.3) 

1 (0.20) 

59 (11.1) 
25 (4.70) 

14 (2.60) 

96 (17.9) 

1 04 (1 9.4) 

22 (4.10) 



G= 16.5 374 (69.9) 145(27.1) 16 (3.00) 
A = 4 1 .8 1 83 (34.2) 25 7 (48.0) 95 ( 1 7.8) 



A = 16.9 



153(28.6) 14 (2.60) 



A = 40.7 188 (35.0) 258(48.0) 89 (17.0) 



0.514 

0.106 

0.949 
0.886 

0.063 

0.833 

0.798 

0.226 
0.798 
0.760 
0.108 
0.698 

0.492 
0.885 
0.752 
0.219 



Table 1 Functional consequence and prevalence of inflammatory-associated sequence variants (Continued) 



Near gene 5' A>C 
TFBS 

Near gene 5' G > A 
TFBS 

Near gene 5' A > G 
TFBS 

rs2192752* IL1R1 Near gene 5' A>C 
TFBS 



rs1 800872" IL10 
rs 1800893* IL10 
rs 1800896* IL10 



rs2227532* IL8 
rs2227538* IL8 
rs2227545* IL8 



Near gene 5' T>C 
TFBS 

UTR'5 C>T 
TFBS, Splicing 

UTR'3 A > C 

miRNA 



rs2229113* IL10RA Exon 7 
nsSNP, 
probably 
damaging 

rs2834167* IL10RB Exon 2 
Splicing, 
nsSNP, 
benign 

rs2856836* ILIA UTR'3 
miRNA 

rs31 35932* IL10RA Exon 5 
Splicing, 
nsSNP, 
benign 



rs31595r 



IL1RN UTR'3 
miRNA 



G > A 

A > G 

T>C 
A > G 

C>G 
T>C 



rs3738579* RNASEL UTR'5 

TFBS, Splicing 

rs3917225* IL1R1 Near gene 5' A > G 
TFBS 



rs4073* 



IL8 



Near gene 5' A>T 
TFBS 



rs4141134" IL1R2 Near gene 5' T>C 

rs4251961* IL1RN Near gene 5' T>C 
TFBS 

rs4252243* IL10RA Near gene 5' C>T 
TFBS 



A = 50.0 
C = 50.0 

A = 37.1 
G = 40.5 
C = 4.80 
C = 9.70 
T= 17.7 
C = 8.70 
A = 20.5 



C = 1 7.4 
G = 2.10 

G = 47.9 

C = 1 6.7 

G = 12.3 

T=26.6 

C = 1 1 .2 
C = 20.2 

T=32.5 



5 (21.7) 
22 (35.5) 
7 (33.3) 
56 (90.3) 
50 (80.6) 
41 (66.1) 
1 9 (82.6) 
14 (63.7) 



1 6 (69.6) 
23 (95.8) 

8 (33.3) 

14 (66.7) 

49 (80.3) 

34 (54.8) 

39 (79.6) 
37 (59.7) 

9 (45.0) 



13 (56.6) 
34 (54.8) 

1 1 (52.4) 

6 (9.70) 

12 (19.4) 
20 (32.3) 
4 (17.4) 

7 (31.8) 



G = 16.9 44(71.0) 15(24.2) 



6 (26.1) 
1 (4.20) 

9 (37.5) 

7 (33.3) 

9 (14.8) 

23 (37.1) 

9 (18.4) 
25 (40.3) 

9 (45.0) 



5 (21.7) 

6 (9.70) 
3 (14.3) 
0 (0.00) 

0 (0.00) 

1 (1.60) 

0 (0.00) 

1 (4.50) 

3 (4.80) 

1 (4.30) 
0 (0.00) 

7 (29.2) 

0 (0.00) 
3 (4.90) 
5 (8.10) 

1 (2.00) 
0 (0.00) 

2 (10.0) 



C > A 
G > A 
A > G 
A>C 
A > G f 
G > A f 
A>C 
G > A 

A > G 

A > G f 

A > G 

C>G 

A > G f 

A > G 

T> A 

A > G f 
A > G f 

G> A f 



A = 40.7 
A = 36.4 
G = 33.3 
C = 5.60 
G = 8.60 
A = 23.2 
C = 8.50 
A = 1 8.8 



188 (35.0) 258 (48.0) 89(17.0) 0.874 

216(40.4) 248(46.4) 71(13.2) 0.419 

243(45.4) 228(42.6) 64(12.0) 0.491 

477(89.1) 56(10.5) 2(0.40) 1.000 

448 (83.7) 82 (15.3) 5(1.00) 0.690 

323 (60.4) 176(32.9) 36(6.70) 0.291 



449 (83.9) 81 (15.1) 5 (1.00) 



G = 1 1 .0 423(79.1) 106(19.8) 6(1.10) 



G = 1 8.6 
G = 2.60 

G = 48.0 

G = 12.3 

G = 9.10 

A = 20.9 

G = 13.7 
G = 1 7.9 



0.812 



355 (66.4) 159 (29.7) 21 (3.90) 0.782 



0.050 



358 (66.9) 155 (29.0) 22 (4.10) 1.000 

508 (95.0) 26 (4.80) 1 (0.20) 1.000 

144 (26.9) 268(50.1) 123 (23.0) 0.482 

411 (76.8) 116 (21.7) 8 (1.50) 0.474 



438(81.9) 97(18.1) 0(0.00) 



0.001 



335 (62.6) 1 76 (32.9) 24 (4.50) 0.262 



399 (74.6) 1 25 (23.4) 1 1 (2.00) 
367 (68.6) 145 (27.1) 23(4.30) 0.035 



A = 27.5 271 (50.7) 234 (43.7) 30 (5.60) 0.522 



Table 1 Functional consequence and prevalence of inflammatory-associated sequence variants (Continued) 



rs4674257 ++ 


IL8RB 


Near gene 5' 
TFBS 


G > A 


A = 


25.0 


14 (58.3) 


8 (33.3) 


2 (8.30) 


G > A 


A = 


20.1 


347 (64.9) 


161 (30.10) 


27 (5.00) 


0.468 


rs4674259 + 


IL8RB 


UTR'5 
TFBS 


A > G 


G = 


23.9 


12 (52.2) 


1 1 (47.8) 


0 (0.00) 


A > G 


G = 


20.0 


349 (65.0) 


1 58 (30.0) 


28 (5.00) 


0.176 


rs486907 + 


RNASEL 


Exon 1 
nsSNP, 
benign 


G > A 


A = 


16.7 


1 6 (66.7) 


8 (33.3) 


0 (0.00) 


G > A 


A = 


13.2 


402 (75.1) 


1 25 (23.4) 


8 (1.50) 


0.528 


rs6726713 + * 


IL1R2 


Near gene 5' 
TFBS 


C>T 


T= 


11.2 


38 (77.6) 


11 (22.4) 


0 (0.00) 


G>A + 


A = 


12.1 


417 (78.0) 


106 (19.8) 


12 (2.20) 


0.689 


rs673* 


TNF 


Near gene 5' 
TFBS 


G > A 


A = 


13.7 


45 (72.6) 


1 7 (27.4) 


0 (0.00) 


G > A 


A = 


17.4 


364 (68.0) 


156 (29.2) 


15 (2.80) 


0.546 


rs8 178433* 


IL10RB 


Near gene 5' 
TFBS 


T> G 


G = 


12.9 


46 (74.2) 


1 6 (25.8) 


0 (0.00) 


A>C t 


C = 


12.4 


408 (76.3) 


121 (22.6) 


6 (1.10) 


0.811 


rs949963* 


IL1R1 


Near gene 5' 
TFBS 


G > A 


A = 


31.1 


31 (50.8) 


22 (36.1) 


8 (13.1) 


G > A 


A = 


33.1 


249 (46.5) 


218 (40.8) 


68 (12.7) 


0.771 


rs9610 + 


IL10RA 


UTR'3 
miRNA 


A > G 


G = 


41.9 


20 (32.3) 


32 (51.6) 


10 (16.1) 


A > G 


G = 


33.9 


237 (44.3) 


233 (43.5) 


65 (12.2) 


0.184 


rs999788* 


IL10RB 


Near gene 5' 
TFBS 


C>T 


T= 


19.5 


40 (67.8) 


1 5 (25.4) 


4 (6.80) 


G>A + 


A = 


12.4 


410 (76.6) 


117 (21.9) 


8 (1.50) 


0.026 



+ The nucleotide change may vary relative to that reported in NCBI depending on whether the genotyping was performed using the sense or anti-sense DNA strand. 

+t The chi-square test was used to assess differences in the overall genotype frequencies comparing men of African Descent as reported in NCBI to those in the total population from the current study. P-values generated from 
the Fisher's exact test (in italics) were used when expected genotype counts were < 5 for either cases or controls. 

Abbreviations: MAF Minor Allele Frequency; UTR untranslated region; TFBS transcription factor binding site; nsSNP non-synonymous coding SNP; miRNA microRNA binding site; NCBI National Center for Biotechnology 
Information Entrez SNP. 

*NCBI AFR1 or African American Population Panel. 
**NCBI ASW Population Panel. 



Jones et al. Hereditary Cancer in Clinical Practice 201 3, 11:19 Page 7 of 1 1 

http://www.hccpjournal.eom/content/1 1/1/19 



Table 2 Relationship between inflammatory related sequence variants and prostate cancer risk among men of 
African Descent 



Genes 


dbSNP ID location 
predicted function 


Genotype 


Cases 
n (%) 


Controls 

n (%) 


Unadjusted 
OR (95%CI) t 


Adjusted 
OR (95%CI) + 


p-value* 


p trend 


Bonferroni 
correction 


IL1R2 


rsl 1886877 


GG 


87 (31.2) 


211 (39.4) 


1 .00 (referent) 


1 .00 (referent) 


0.034 


0.010 


NS 




Intron 1 


GA 


149 (53.4) 


265 (49.5) 


1 .36 (0.99, 1 .88) 


1.35 (0.92,1.98) 


0.058 










AA 


43 (1 5.4) 


59 (11.1) 


1.77 (1.11, 2.82) 


1.92 (1.11, 3.32) 


0.017 










GA + AA 


1 92 (68.8) 


324 (60.6) 


1.44 (1.06, 1.95) 


1.46 (1.01, 2.10) 


0.021 










AA vs (GG + GA) 






1 .47 (0.96,2.24) 


1.61 (0.98,2.63) 


0.074 






ILIA 


rs17561 


CC 


1 95 (69.9) 


358 (66.9) 


1 .00 (referent) 


1 .00 (referent) 


0.025 


0.108 


NS 




Exon 4 


CA 


82 (29.4) 


1 55 (29.0) 


0.97 (0.70,1.34) 


1.01 (0.68,1.48) 


0.858 








Splicing 


AA 


2 (0.70) 


22 (4.10) 


0.17 (0.04, 0.72) 


0.40 (0.08,1.83) 


0.016 








nsSNP 


GA + AA 


84 (30.1) 


177 (33.1) 


0.87 (0.64,1.20) 


0.96 (0.66,1.40) 


0.388 








benign 


AA vs (CC + CA) 






0.17 (0.04, 0.72) 


0.40 (0.09,1.82) 


0.016 






IL8RB 


rs 11574752 


GG 


230 (82.4) 


435 (81.3) 


1 .00 (referent) 


1 .00 (referent) 


0.011 


0.784 


NS 




3'-UTR 


GA 


43 (1 5.4) 


99 (18.5) 


0.82 (0.55,1.21) 


0.90 (0.56,1.40) 


0.326 








miRNA 


AA 


6 (2.20) 


1 (0.20) 


11.3 (1.36, 94.6) 


38.4 (3.86, 382.8) 


0.009 










GA + AA 


49 (17.6) 


100 (18.7) 


0.93 (0.64,1.35) 


1.08 (0.69,1.70) 


0.693 










AA vs (GG + GA) 






11.7 (1.40, 98.0) 


39.2 (3.94, 390) 


0.008 






TNF 


rs 1800629 


GG 


171 (61.2) 


368 (68.8) 


1 .00 (referent) 


1 .00 (referent) 


0.047 


0.087 


NS 




5' near gene 


GA 


1 03 (37.0) 


1 53 (28.6) 


1.45 (1.06, 1.97) 


1 .54 (1 .06, 2.24) 


0.019 








TFBS 


AA 


5 (1 .80) 


14 (2.60) 


0.77 (0.27, 2.16) 


1 .30 (0.37,4.60) 


0.619 










GA + AA 


108 (38.8) 


167 (31.2) 


1.39 (1.03, 1.90) 


1.53 (1.06, 2.20) 


0.032 










AA vs (GG + GA) 






0.68 (0.24,1.91) 


1.13 (0.32,3.90) 


0.462 






TNF 


rs673 


GG 


171 (61.3) 


364 (68.0) 


1 .00 (referent) 


1 .00 (referent) 


0.009 


0.228 


NS 




5' near gene 


GA 


106 (38.0) 


156 (29.2) 


1.45 (1.06, 2.00) 


1.50 (1.04, 2.16) 


0.018 








TFBS 


AA 


2 (0.70) 


1 5 (2.80) 


0.28 (0.06, 1 .26) 


0.47 (0.09,2.40) 


0.097 










GA + AA 


108 (39.1) 


171 (32.0) 


1 .34 (0.99, 1 .82) 


1.43 (1.00, 2.05) 


0.055 










AA vs (GG + AG) 






0.25 (0.06,1.10) 


0.41 (0.08,2.07) 


0.067 






ILIA 


rs2856836 


AA 


196 (70.3) 


358 (66.9) 


1 .00 (referent) 


1 .00 (referent) 


0.024 


0.089 


NS 




3'-UTR 


AG 


81 (29.0) 


1 55 (29.0) 


0.96 (0.69,1.32) 


0.99 (0.67,1.45) 


0.776 








miRNA 


GG 


2 (0.70) 


22 (4.10) 


0.17 (0.04, 0.71) 


0.40 (0.09,1.82) 


0.016 










AG + GG 


83 (29.7) 


177 (33.1) 


0.86 (0.63,1.17) 


0.94 (0.65,1.36) 


0.333 










GG vs (AA + AG) 






0.17 (0.04, 0.72) 


0.40 (0.09,1.82) 


0.016 






IL10RA 


rs4252243 


GG 


1 34 (48.4) 


268 (50.4) 


1 .00 (referent) 


1 .00 (referent) 


0.066 


0.168 


NS 




5' near gene 


GA 


115 (41.5) 


234 (44.0) 


0.98 (0.72,1.32) 


0.83 (0.58,1.18) 


0.893 








TFBS 


AA 


28 (10.1) 


30 (5.60) 


1.86 (1.07, 3.24) 


1.62 (0.82, 3.21) 


0.028 










GA + AA 


143 (51.6) 


264 (49.6) 


1.08 (0.81,1.44) 


0.91 (0.64,1.28) 


0.605 










AA vs (GG + GA) 






1.88 (1.10, 3.21) 


1.77 (0.91, 3.43) 


0.021 







+ On a separate line before the text regarding the chi-square test p-values state the following: 

f Boldface odd ratios (ORs) and 95% confidence interval (CI) indicate a significant relationship between the selected SNPs and prostate cancer risk. 
From top to bottom within the column, the chi-square test p-values were used to determine the difference in the genotype frequencies between cases and 
controls for the overall, minor/major versus major/major genotypes, as well as the dominant (i.e., minor/minor versus major/major), co-dominant (minor/minor + 
major/minor versus major/major), and recessive genetic models (minor/minor versus major/major + major/minor). P-values generated from the Fisher's Exact test 
(in italics) were calculated when expected genotype counts were < 5 for either cases or controls. Statistically significant p-values are marked in bold face. 
Abbreviations: (777?, untranslated region; TFBS, transcription factor binding site; miRNA, microRNA binding site; NS, non-significant. 



Table 3 Relationship between inflammatory related sequence variants and prostate cancer risk among U.S. and Jamaican men 



Genes 


dbSNP ID location 
predicted function 


Genotype 


Unadjusted OR 
(95%CI) US ment 


Age-adjusted OR 
(95%CI) US ment 


Unadjusted OR 
(95%CI) Jamaican ment 


Age-adjusted OR 
(95%CI) Jamaican ment 


p-value 
US men* 


p-value 
Jamaican men* 


p-trend 
US men 


p-trenc 
Jamaican 


IL1B 


rs1071676 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.050 


0.550 


0.022 


0.2/6 




UTR'3 


GC 


0.72 (0.48, 1.10) 


0.70 (0.42, 1.14) 


1.39 (0.71, 2.70) 


1 .28 (0.62, 2.64) 


0.124 


0.338 








miRNA 


CC 


0.16 (0.02, 1.25) 


0.19 (0.02, 2.00) 


2.02 (0.18, 22.8) 


1.15 (0.10, 14.6) 


0.035 


0.500 










GC + CC 


0.66 (0.44, 1 .00) 


0.66 (0.40, 1.10) 


1 .42 (0.74, 2.72) 


1 .26 (0.62, 2.60) 


0.050 


0.294 










CC vs (GG + GC) 


0.18 (0.02, 1.36) 


0.21 (0.02, 2.18) 


1.89 (0.16, 21.1) 


1.10 (0.08, 13.7) 


0.046 


0.525 






IL1B 


rs1 143634 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.051 


0.447 


0.016 


0.203 




Exon 4 


GA 


0.67 (0.44, 1.01) 


0.65 (0.40, 1 .06) 


1.51 (0.76, 3.00) 


1.37 (0.64, 2.90) 


0.058 


0.243 








Splicing 


AA 


0.21 (0.02, 1.60) 


0.24 (0.02, 2.86) 


2.05 (0.18, 23.0) 


1.16 (0.10, 14.6) 


0.080 


0.496 










GA + AA 


0.63 (0.42, 0.95) 


0.62 (0.38, 1 .02) 


1 .54 (0.78, 3.00) 


1 .36 (0.65, 2.82) 


0.028 


0.208 








cds-synonymous 


AA vs (GG + GA) 


0.23 (0.02, 1 .80) 


0.27 (0.02, 3.20) 


1.89 (0.16, 21.1) 


1.10 (0.08, 13.7) 


0.105 


0.525 






IL1R2 


rs 11886877 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.007 


0.889 


0.002 


0.631 




ntron 1 


GA 


1.60 (1.08, 2.40) 


1.63 (1.00, 2.64) 


0.92 (0.50, 1 .68) 


0.94 (0.48, 1 .80) 


0.020 


0.782 










AA 


2.34 (1.31, 4.16) 


2.75 (1.38, 5.50) 


0.82 (0.36, 1 .86) 


0.94 (0.38, 2.30) 


0.004 


0.633 










GA + AA 


1.72 (1.18, 2.52) 


1.82 (1.14, 2.88) 


0.89 (0.50, 1 .58) 


0.94 (0.50, 1 .74) 


0.005 


0.700 










AA vs (GG + GA) 


1.76 (1.04, 2.96) 


2.05 (1.10, 3.80) 


0.86 (0.40, 1 .80) 


0.97 (0.43, 2.20) 


0.033 


0.691 






RNASEL 


rsl 21 35247 


AA 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.800 


0.025 


0.909 


0.216 




UTR'3 


AG 


1 .06 (0.72, 1 .58) 


1.14 (0.71, 1.84) 


2.17 (1.14,4.12) 


2.10 (1.04, 4.24) 


0.756 


0.018 








TFBS 


GG 


0.77 (0.30, 1 .96) 


0.70 (0.24, 2.10) 


0.45 (0.08, 2.40) 


0.28 (0.04, 1 .70) 


0.570 


0.284 








miRNA 


AG + GG 


1 .02 (0.70, 1 .50) 


1 .07 (0.68, 1 .68) 


1.81 (0.99, 3.30) 


1 .68 (0.88, 3.24) 


0.906 


0.053 










GG vs (AG + AA) 


0.76 (0.30, 1.92) 


0.67 (0.22, 1 .97) 


0.36 (0.06, 1.91) 


0.22 (0.04, 1 .35) 


0.555 


0.196 






TNF 


rsl 800629 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.101 


0.782 


0.113 


0.549 




5' near gene 


GA 


1.50 (1.03, 2.20) 


1 .52 (0.96, 2.42) 


1.21 (0.68, 2.12) 


1.41 (0.78, 2.63) 


0.034 


0.518 








TFBS 


AA 


0.90 (0.28, 2.80) 


1.51 (0.36, 6.24) 


1.00 (0.06, 16.3) 


1 .00 (0.06, 1 7.2) 


0.551 


0.752 










GA + AA 


1.44 (0.99, 2.10) 


1 .53 (0.97, 2.40) 


1.20 (0.68, 2.10) 


1 .40 (0.75, 2.60) 


0.050 


0.525 










AA vs (GG + GA) 


0.78 (0.25, 2.42) 


1 .32 (0.32, 5.40) 


0.94 (0.06, 1 5.2) 


0.88 (0.05, 15.0) 


0.452 


0.734 






ILIA 


rsl 800587 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.088 


0.450 


0.028 


0.224 




UTR'5 


GA 


0.75 (0.50, 1.10) 


0.68 (0.42, 1 .08) 


1 .38 (0.76, 2.50) 


1 .42 (0.74, 2.72) 


0.144 


0.297 








TFBS 


AA 


0.56 (0.32, 0.96) 


0.78 (0.40, 1 .53) 


1 .56 (0.69, 3.50) 


1 .64 (0.70, 4.00) 


0.038 


0.279 








Splicing (ESE or 


GA + AA 


0.70 (0.48, 1 .00) 


0.70 (0.45, 1.10) 


1 .42 (0.80, 2.50) 


1 .47 (0.80, 2.72) 


0.053 


0.222 








ESS) 


AA vs (GG + GA) 


0.66 (0.40, 1.10) 


0.96 (0.52, 1 .80) 


1 .30 (0.62, 2.70) 


1 .34 (0.60, 3.00) 


0.105 


0.478 






MORA 


rs4252243 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.062 


0.620 


0.275 


0.329 



Table 3 Relationship between inflammatory related sequence variants and prostate cancer risk among U.S. and Jamaican men (Continued) 



5' near gene 


GA 


0.92 (0.63, 1.33) 


0.70 (0.44, 1.10) 


1 .24 (0.70, 2.20) 


1.21 (0.64, 2.28) 


0.648 


0.448 




TFBS 


AA 


2.02 (1 .04, 3.95) 


2.10 (0.90, 4.98) 


1 .50 (0.54, 4.26) 


1 .04 (0.34, 3.20) 


0.038 


0.436 






GA + AA 


1.03 (0.72, 1.50) 


0.81 (0.52, 1.30) 


1.28 (0.74, 2.21) 


1.15 (0.64, 2.10) 


0.863 


0.328 






AA vs (GG + GA) 


2.11 (1.10, 4.02) 


2.49 (1.08, 5.72) 


1.37 (0.50, 3.74) 


1 .02 (0.40, 2.98) 


0.023 


0.539 




TNF rs673 


GG 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


1 .00 (referent) 


0.027 


0.452 


0.279 0.874 


5' near gene 


GA 


1.50 (1.02, 2.20) 


1 .46 (0.92, 2.30) 


1.22 (0.70, 2.14) 


1.41 (0.76, 2.62) 


0.025 


0.498 




TFBS 


AA 


0.24 (0.03, 1 .84) 


0.54 (0.06, 4.44) 


0.33 (0.03, 3.24) 


0.40 (0.03, 4.70) 


0.116 


0.315 






GA + AA 


1 .38 (0.95, 2.00) 


1 .40 (0.88, 2.20) 


1.14 (0.66, 2.00) 


1 .33 (0.72, 2.46) 


0.087 


0.635 






AA vs (GG + GA) 


0.21 (0.02, 1.60) 


0.47 (0.06, 3.91) 


0.31 (0.03, 2.98) 


0.35 (0.03, 4.08) 


0.080 


0.286 





On a separate line before the text regarding the chi-square test p-values state the following: 

tBoldface odd ratios (ORs) and 95% confidence interval (CI) indicate a significant relationship between the selected SNPs and prostate cancer risk. 

*From top to bottom within the column, the chi-square test p-values were used to determine the difference in the genotype frequencies between cases and controls for the overall, minor/major versus major/major ge- 
notypes, as well as the dominant (i.e., minor/minor versus major/major), co-dominant (minor/minor + major/minor versus major/major), and recessive genetic models (minor/minor versus major/major + major/minor). 
P-values generated from the Fisher's Exact test (in italics) were calculated when expected genotype counts were < 5 for either cases or controls. Statistically significant p-values are marked in bold face. 
Abbreviations: UTR, untranslated region; TFBS, transcription factor binding site; cds-syn, synonymous SNP; miRNA, microRNA binding site. 



Jones et al. Hereditary Cancer in Clinical Practice 2013, 11:19 
http://www.hccpjournal.eom/content/1 1/1/19 



Page 1 0 of 1 1 



mesenchymal transition (EMT), by binding to IL1R2 to 
increase prostate cancer tumorigenesis [30]. 

Out of 44 inflammatory-related sequence variants, 7 
SNPs included in our study were evaluated in relation 
to prostate cancer outcomes within 4 independent observa- 
tional studies [6,7,10,11]. Commensurate with our findings, 
two observational studies demonstrated that sequence 
variants detected in IL10 (rsl800871, rsl800872) and IL8 
rs4073 were not significantly related to prostate cancer risk 
[6,11]. Inheritance of the TNF rsl800629 AA genotype was 
associated with a significant 1.8 fold increase in prostate 
cancer risk among Caucasian men in a small study (150 
cases, 150 controls); however, this marker resulted in null 
findings in a larger study (468 cases, 468 controls) [6,7]. In 
our preliminary analyses, inheritance of one or more TNF 
rsl800629 A alleles was marginally associated with a 
1.5-fold increase in prostate risk; however, this relation- 
ship did not survive adjustment after multiple hypothesis 
testing. Lastly, IL10 rsl800896 G and IL1B rsl 143627 C 
alleles had protective effects in two separate Caucasian sub- 
populations. However, neither of these markers were signifi- 
cantly related to prostate cancer among African- American 
men in the current study. Casey and colleagues (2002) 
showed a 2-fold increase in prostate cancer susceptibility 
linked to inheritance of the RNASEL rs486907 AA geno- 
type among mostly men of European descent [10]. This 
locus was not related to prostate cancer risk among 
African- Americans in the current study. Racial/ethnic dis- 
parities in the aforementioned risk estimates may be attrib- 
uted to differences in minor allele frequencies, failure to 
adjust findings for multiple hypothesis testing or inadequate 
sample size among men with African ancestry. 

In this study, we considered the strengths, limitations 
and future directions of the project. Forty-four sequence 
variants were evaluated in relation to prostate cancer risk 
among men of African Descent from the U.S. and Jamaica. 
Upon stratification by study center, the IL1R2 rsl 1886877 
locus was marginally related to prostate cancer among 
men of African descent from the U.S. However, overall the 
inflammatory-related sequence variants were not robustly 
related to prostate cancer among our study participants. 
Despite this, we cannot eliminate the possibility that IL1R2 
and other inflammatory-related sequence variants not 
included in this study may influence the risk of prostate 
cancer development or aggressive tumor behavior. In 
larger studies, the impact of individual or interaction 
among inflammatory cytokine-associated sequence vari- 
ants in relation to prostate cancer tumor grade, biochem- 
ical or disease recurrence, and mortality using targeted 
sequencing, in vitro studies, in silico and bioinformatics 
tools. Such efforts will help to identify genetic markers 
linked to disproportionately high prostate cancer 
incidence, mortality, and morbidity rates among men of 
African Descent. Population admixture, which commonly 



occurs among men of African descent, may bias risk esti- 
mates. However, adjustment of risk estimates by West 
African Ancestry and/or age did not significantly modify 
the directionality of observed risk estimates among men 
from the U.S. (data not shown). Although, the sample 
size of this study population is small, there was ample 
statistical power to accurately detect risk estimates, 
ranging between 1.4-1.8 or 0.55-0.70. Our findings are 
important to genetic epidemiology research teams inter- 
ested in pooling genetic and tumor characteristic data to 
determine whether other variant inflammatory-related 
cytokines contribute to prostate cancer susceptibility and 
disease prognosis. Although this study displays a modest 
association between inflammatory-related cytokine variant 
IL1R2 rsl 1886877 and prostate cancer risk, this relation- 
ship has yet to be tested biologically. The association of 
IL1R2 rsl 1886877 with prostate cancer risk may prove to 
be strong in a larger study population. 

Conclusions 

Chronic inflammation is an established risk factor of 
prostate cancer and many studies argue that it can lead 
to prostate cancer development. In this study, 44 
inflammatory-related cytokine variants that may play a 
role in chronic inflammation were analyzed in relation 
to prostate cancer risk. Our preliminary data suggests that 
the possession of IL1R2 rsl 1886877 locus modifies prostate 
cancer susceptibility among individuals with African ances- 
try in the U.S. However, the association of the IL1R2 variant 
with prostate risk did not remain significant after adjust for 
multiple hypothesis testing. Future studies with ample stat- 
istical power to accommodate adjustment for multiple 
comparisons bias, will enable us to evaluate the impact 
of the IL1R2 variant or a combination of inflammatory 
cytokine SNPs in relation to prostate cancer risk, tumor 
grade, biochemical or disease recurrence, and mortality. 
These studies will lead to the identification of genetic 
markers that modify the susceptibility of individuals. 

Abbreviations 

SNP: Single nucleotide polymorphism; LR: Logistic regression. 
Competing interests 

The authors declare that they have no competing interests. 
Authors' contributions 

LRK and KSK: conceptualized the project. LRK, KSK, CR, MJ, NM, MT, SM: 
participated in the study design. DZJ, LRK: composed the manuscript. DZJ, 
LRK, CR, REF: revised subsequent manuscript drafts. DZJ, NCK: quality control 
and statistical analysis. LRK: supervised quality control analysis, data-management 
and statistical analysis. LRK, DZJ, CR, KSK: interpreted the data, gave 
important intellectual input toward the introduction, results and/or 
discussion. All co-authors: read and edited the manuscript drafts as well 
as gave final approval of the final manuscript draft. 

Acknowledgements 

We thank Tiva T. VanCleave and Nicole A. Lavender for DNA sample 
preparation. We appreciate the contract services of Expression Analysis, Inc. 
(http://www.expressionanalysis.com) for the generation of genotype data. 



Jones et al. Hereditary Cancer in Clinical Practice 2013, 11:19 
http://www.hccpjournal.eom/content/1 1/1/19 



Page 11 of 1 1 



We offer gratitude to Dr. Rick Kittles for the donation of DNA samples from 
prostate cancer patients. 

Lastly, we value Peter Andrews for his service as a computer programming 
consultant on this project. 

Grant/Research support: Clinical Translational Science Pilot Grant to LRK; the 
JGBCC Bucks for Brains "Our Highest Potential" in Cancer Research 
Endowment to LRK; P20-MD0001 75 NIH NCMHD to KSK. 

Author details 

'Department of Pharmacology & Toxicology, University of Louisville, 
Louisville, KY, USA. 2 Cancer Prevention and Control Program, Fox Chase 
Cancer Center, Philadelphia, PA, USA. 3 Molecular and Cellular Biology 
Program, State University of New York, Brooklyn, NY, USA. department of 
Community Health and Psychiatry, University of West Indies, Mona, Kingston, 
Jamaica, department of Basic Medical Sciences, University of the West 
Indies, Mona Campus, Kingston, Jamaica, tropical Medicine Research 
Institute, University of the West Indies, Mona, Kingston, Jamaica. 'Biomedical/ 
Biotechnology Research Institute (BBRI), North Carolina Central University, 
Durham, NC, USA. 

Received: 29 July 2013 Accepted: 3 December 2013 
Published: 23 December 2013 



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doi:1 0.1 1 86/1 897-4287-1 1-19 

Cite this article as: Jones ef al: The impact of genetic variants in 
inflammatory-related genes on prostate cancer risk among men of African 
Descent: a case control study. Hereditary Cancer in Clinical Practice 
2013 11:19. 



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